Colchicine for the Prevention of Post-Operative Atrial Fibrillation After Coronary Artery Bypass Grafting: A Single-Center, Strategy-Stratified, Randomized, Double-Blind, Placebo-Controlled Trial

Randomized, Double-Blind, Placebo-Controlled Trial of Colchicine to Prevent Post-Operative Atrial Fibrillation After CABG With Strategy-Stratified Randomization

Post-operative atrial fibrillation after coronary artery bypass grafting (CABG)

Study Overview

• Status: Not yet recruiting
• Conditions: Post-Operative Atrial Fibrillation After Coronary Artery Bypass Grafting (CABG)
• Intervention / Treatment: Drug: Colchicine 0.5 MG oral tablet twice daily; Drug: Placebo Oral Tablet

Detailed Description

This single-center, prospective, randomized, double-blind, placebo-controlled clinical trial aims to evaluate the efficacy of colchicine in preventing post-operative atrial fibrillation (POAF) following coronary artery bypass grafting (CABG) and to compare its pharmacologic and clinical effects between different surgical strategies - off-pump CABG (OPCAB) and on-pump CABG (ONCAB).

Post-operative atrial fibrillation is one of the most common arrhythmias after CABG, with an incidence of approximately 50%, and is associated with prolonged ICU and hospital stay and increased healthcare utilization. Intravenous amiodarone is commonly used for POAF treatment but may increase the risk of catheter-related infection. Colchicine, an anti-inflammatory and immunomodulatory agent, has shown potential to reduce postpericardiotomy syndrome and POAF in small-scale studies, but existing evidence remains inconsistent, and most prior trials did not distinguish between surgical strategies.

In this trial, 400 adult patients undergoing elective CABG will be enrolled and randomized in a 1:1 ratio within each stratum (OPCAB and ONCAB) to receive either colchicine or placebo. The treatment group will receive colchicine 0.5 mg orally twice daily, starting on postoperative day -3 and continuing through postoperative day 7. The placebo group will receive identically appearing tablets on the same schedule.

The primary endpoint is the incidence of new-onset atrial fibrillation within 14 days after surgery, defined as any episode lasting ≥30 seconds documented by 12-lead ECG, continuous telemetry, or Holter monitoring.

Secondary outcomes include the incidence and management of other arrhythmias (atrial flutter, supraventricular tachycardia), total dose and duration of intravenous amiodarone, ICU and total hospital length of stay, ischemic stroke or TIA, infection events (including catheter-related infection), and 30-day readmission. Safety outcomes will include gastrointestinal intolerance, hepatic enzyme elevation, creatine kinase elevation with myalgia, hematologic abnormalities, and serious adverse events (SAE).

Pharmacokinetic (PK) and pharmacodynamic (PD) analyses will measure colchicine concentrations in plasma and pericardial fluid and correlate these with inflammatory biomarkers (CRP, IL-6, TNF-α, white blood cell profile, and immune cell phenotyping by flow cytometry). This integrated approach aims to elucidate the relationship between colchicine exposure, inflammation, and POAF occurrence.

Statistical analyses will primarily follow an intention-to-treat (ITT) approach. The primary endpoint will be evaluated using a log-binomial or Poisson-robust model to estimate relative risk (RR) with 95% confidence intervals, including treatment, surgical strategy, and their interaction terms. Time-to-event outcomes will be analyzed using Cox proportional hazards or Kaplan-Meier methods, and continuous variables by linear mixed-effects models. Missing data will be handled conservatively with multiple imputation where appropriate. An independent Data and Safety Monitoring Board (DSMB) will review blinded safety data once 50% of subjects have been enrolled.

The trial is expected to clarify the pharmacokinetic and clinical effects of colchicine in different CABG surgical strategies. If colchicine is shown to effectively reduce POAF in OPCAB patients or in those achieving sufficient plasma concentrations, it may provide a simple, low-cost preventive strategy that reduces the need for intravenous amiodarone, lowers infection risk, and shortens ICU and hospital stay. The results could guide future optimization of dosing and timing strategies in ONCAB patients and improve perioperative management and resource utilization in cardiac surgery.

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Jeng-Wei Chen, MD; Phone Number: +886-2-2312-3456 ext. 265081; Email: chenjw@ntu.edu.tw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults aged 20 years or older scheduled to undergo elective coronary artery bypass grafting (CABG), including either off-pump CABG or on-pump CABG.
• Ability to receive oral study medication before and after surgery.
• Provision of written informed consent before randomization.

Exclusion Criteria:

• History of atrial fibrillation or atrial flutter before surgery.
• Severe renal impairment (estimated glomerular filtration rate <30 mL/min/1.73 m²) or chronic dialysis.
• Severe hepatic dysfunction.
• Known hypersensitivity or previous severe adverse reaction to colchicine.
• Pregnancy or breastfeeding.
• Current use of strong CYP3A4 or P-glycoprotein inhibitors that cannot be safely discontinued or substituted.
• Any condition judged by the investigators to interfere with study participation or safety assessment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Colchicine Group; Participants will receive colchicine 0.5 mg orally twice daily starting 3 days before surgery and continuing through postoperative day 7 under double-blind conditions. Randomization is stratified by surgical strategy (off-pump CABG versus on-pump CABG).	Drug: Colchicine 0.5 MG oral tablet twice daily; Colchicine 0.5 mg administered orally twice daily beginning 3 days before surgery and continuing through postoperative day 7. Temporary interruption or discontinuation is permitted for clinically significant adverse events according to the study safety protocol.
Placebo Comparator: Placebo Group; Participants will receive an identically appearing placebo tablet orally twice daily starting 3 days before surgery and continuing through postoperative day 7 under double-blind conditions. Randomization is stratified by surgical strategy (off-pump CABG versus on-pump CABG).	Drug: Placebo Oral Tablet; Matching placebo tablet administered orally twice daily beginning 3 days before surgery and continuing through postoperative day 7 under double-blind conditions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of new-onset atrial fibrillation within 14 days after CABG surgery	New-onset atrial fibrillation (AF) or atrial flutter (AFL) lasting ≥30 seconds, documented by 12-lead ECG, continuous telemetry monitoring, or 24-hour Holter recording, occurring within 14 days after coronary artery bypass grafting (CABG). Events are adjudicated by blinded cardiologists according to prespecified criteria.	From the day of surgery through postoperative day 14.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total duration of post-operative atrial fibrillation (POAF)	Cumulative duration (in hours) of all atrial fibrillation or atrial flutter episodes documented by telemetry or ECG monitoring within 14 days after surgery.	From the day of surgery through postoperative day 14.
Proportion of patients requiring cardioversion for POAF	Percentage of patients who undergo pharmacologic or electrical cardioversion for atrial fibrillation/flutter occurring within 14 days after surgery.	From the day of surgery through postoperative day 14.
Total dose of intravenous amiodarone used for POAF treatment	Total cumulative intravenous amiodarone dose (mg) administered for POAF management during the first 14 postoperative days.	From the day of surgery through postoperative day 14.
Length of stay in the intensive care unit (ICU)	Duration (days) of ICU hospitalization from the date of surgery until discharge from the intensive care unit.	From the date of surgery until discharge from the intensive care unit or death, whichever occurred first, assessed up to 30 days after surgery.
Total hospital length of stay	Total number of days from hospital admission for CABG surgery until hospital discharge.	From hospital admission until hospital discharge or death, whichever occurred first, assessed up to 60 days after surgery.
30-day hospital readmission	Incidence of unplanned hospital readmission for any cause within 30 days after discharge from index CABG hospitalization.	From hospital discharge until 30 days after discharge.
Plasma and pericardial fluid colchicine concentrations	Measured colchicine concentrations (ng/mL) in plasma and pericardial fluid at predefined perioperative time points(preoperative baseline, end of surgery, postoperative day 1, postoperative day 3, and postoperative day 7)for pharmacokinetic analysis.	From preoperative day 1 through postoperative day 7.

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital

Publications and helpful links

General Publications

• Imazio M, Brucato A, Ferrazzi P, Rovere ME, Gandino A, Cemin R, Ferrua S, Belli R, Maestroni S, Simon C, Zingarelli E, Barosi A, Sansone F, Patrini D, Vitali E, Trinchero R, Spodick DH, Adler Y; COPPS Investigators. Colchicine reduces postoperative atrial fibrillation: results of the Colchicine for the Prevention of the Postpericardiotomy Syndrome (COPPS) atrial fibrillation substudy. Circulation. 2011 Nov 22;124(21):2290-5. doi: 10.1161/CIRCULATIONAHA.111.026153. Epub 2011 Nov 16.
• Zhao H, Chen Y, Mao M, Yang J, Chang J. A meta-analysis of colchicine in prevention of atrial fibrillation following cardiothoracic surgery or cardiac intervention. J Cardiothorac Surg. 2022 Sep 1;17(1):224. doi: 10.1186/s13019-022-01958-9.
• Wang MX, Deng XL, Mu BY, Cheng YJ, Chen YJ, Wang Q, Huang J, Zhou RW, Huang CB. Effect of colchicine in prevention of pericardial effusion and atrial fibrillation: a meta-analysis. Intern Emerg Med. 2016 Sep;11(6):867-76. doi: 10.1007/s11739-016-1496-5. Epub 2016 Jul 4.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: February 24, 2026
• First Submitted That Met QC Criteria: May 20, 2026
• First Posted (Actual): May 28, 2026

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: pharmacokinetics; inflammation; cardiopulmonary bypass; coronary artery bypass grafting; neutrophil extracellular traps; colchicine; postoperative atrial fibrillation; off-pump surgery
• Additional Relevant MeSH Terms: Pathologic Processes; Pathological Conditions, Signs and Symptoms; Inflammation; Heterocyclic Compounds; Alkaloids; Colchicine
• Other Study ID Numbers: 202509059MIND

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The individual participant data (IPD) collected in this study will not be shared because they include sensitive clinical and biological information linked to hospital medical records. Data sharing is restricted by institutional and national privacy regulations. Only de-identified, aggregate summary data will be available in publications or presentations after study completion.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No